Non-invasive quantification of liver health in NASH (N-QUAN): A prospective diagnostic accuracy study

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Abstract Non-alcoholic steatohepatitis (NASH) can lead to severe outcomes including decompensated cirrhosis (i.e. advanced liver disease), increased risk of heart disease and liver cancer, and there are no treatments available. Liver biopsy is currently the only approved test for trial inclusion and endpoint assessment in NASH clinical trials, which is invasive, costly, unreliable, is insensitive to disease heterogeneity and unacceptable to many patients. In this project, Perspectum seeks to complete the necessary evidence to qualify the MRI derived biomarker iron-corrected T1 (cT1) as a diagnostic enrichment biomarker, used in conjunction with clinical risk factors, to identify patients who are more likely to have liver histopathologic findings appropriate for inclusion in NASH clinical trials. cT1 has shown promise as an enrichment biomarker and could reduce the use of liver biopsy, by discriminating NASH patients with NAS≥4 & F≥2 on histopathology, from those without. With the funding from this U01 Cooperative Agreement proposal and leveraging the close collaboration with the FDA, we will complete a biopsy-paired single-gate, prospective, cross- sectional, observational study in 225 patients. The objectives for cT1 in this study are two-fold and interdependent: · To evaluate, in patients with suspected NASH referred for Liver biopsy, the diagnostic performance of cT1 at discriminating those NASH patients with NAS≥4 & F≥2 from those without. · To assess the correlation between cT1 and histopathological features of NASH. The study will be carried out at multiple sites including Icahn School of Medicine at Mount Sinai, Liver Center of Texas, University of Virginia, Virginia Commonwealth University, Rush University Chicago, and Arizona Liver Health who will include a representative sample of their patient population over the study duration.